Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Bone. 2018 Sep;114:137-143. doi: 10.1016/j.bone.2018.06.010. Epub 2018 Jun 15.
Emerging evidence indicates that microRNAs (miRNAs, miRs) play diverse roles in the regulation of biological processes, including osteoblastic differentiation. In this study, we found that miR-383 is a critical regulator of osteoblastic differentiation. We showed that miR-383 was downregulated during osteoblastic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). Overexpression of miR-383 suppressed osteoblastic differentiation of BMSCs by downregulating alkaline phosphatase (ALP), matrix mineralization, and mRNA and protein levels of RUNX2 and OCN, whereas a knockdown of miR-383 promoted osteoblastic differentiation in vitro. The results of in vivo analysis indicated that inhibition of miR-383 expression enhanced the efficacy of new bone formation in a rat calvarial defect model. Mechanistic experiments revealed that special AT-rich-sequence-binding protein 2 (Satb2) was a direct and functional target of miR-383. Knockdown of Satb2 had inhibitory effects resembling those of miR-383 on the osteoblast differentiation of rat BMSCs. In addition, the positive effect of miR-383 suppression on osteoblastic differentiation was apparently abrogated by Satb2 silencing. Collectively, these results indicate that miR-383 plays an inhibitory role in osteogenic differentiation of rat BMSCs and may act by targeting Satb2.
新出现的证据表明，microRNAs（miRNAs，miRs）在生物过程的调节中发挥着多样化的作用，包括成骨细胞分化。在这项研究中，我们发现 miR-383 是成骨细胞分化的关键调节因子。我们表明，miR-383 在大鼠骨髓间充质干细胞（BMSCs）的成骨细胞分化过程中下调。miR-383 的过表达通过下调碱性磷酸酶（ALP）、基质矿化以及 RUNX2 和 OCN 的 mRNA 和蛋白水平，抑制 BMSCs 的成骨细胞分化，而 miR-383 的敲低则促进体外成骨细胞分化。体内分析结果表明，抑制 miR-383 的表达增强了新骨形成在大鼠颅骨缺损模型中的疗效。机制实验表明，富含特殊 AT 的序列结合蛋白 2（Satb2）是 miR-383 的直接和功能靶标。Satb2 的敲低对大鼠 BMSCs 的成骨细胞分化具有类似于 miR-383 的抑制作用。此外，Satb2 沉默明显削弱了 miR-383 抑制对成骨细胞分化的正向作用。总之，这些结果表明 miR-383 在大鼠 BMSCs 的成骨细胞分化中发挥抑制作用，可能通过靶向 Satb2 发挥作用。
